Correct!
1. Nothing needs to be done
2. Begin dexamethasone
3. Begin cyclosporine
4. Begin etoposide
The diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH) in children is shown in Table 1 (3).
Table 1. Diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH).
The diagnosis based upon 2004 criteria depends on 5 of 8 criteria. Unfortunately, it is unclear if these criteria also apply in adults and there are no experimental data to guide the treatment of adults with secondary HLH (4-7). Treatments that have been used in adults mimic those for children. It is unknown what the optimal treatment regimen contains, but the 2004 protocol calls for dexamethasone, etoposide, and cyclosporine (3). The high mortality of HLH, often quoted above 90%, has been shown in some observational studies to drop to 40% with early etoposide treatment (3-7). The problem with our patient is that etoposide needs to be used with caution in patients with renal failure, hyperbilirubinemia and hypoalbuminemia (2-6). We have tried to overcome these limitations with reduced etoposide doses and albumin infusions but without successful outcomes (4).
After lengthy discussion of risks and benefits, the family agreed to proceed with treatment for HLH with low dose of etoposide (50 mg/m2), followed by scheduled dexamethasone (10 mg/m2 BID) and cyclosporine (6 mg/kg) per HLH 2004 protocol. He became more hemodynamically stable and weaned off vasopressors but hepatic functions deteriorated. Repeat bone marrow biopsy on day 10 demonstrated resolving hemophagocytosis but persistent histoplasmosis. Unfortunately, on day 12 the patient expired.
The clinical presentation of disseminated histoplasmosis overlaps with the presentation of HLH syndrome, including hepatosplenomegaly, pancytopenia, hepatitis, elevated LDH and ferritin, and fevers, making the distinction difficult.
HLH can be primary, from gene mutations found mainly in pediatric patients, or secondary, triggered most commonly by infections and autoimmune disorders (3). HLH is a disorder of NK and CD8+ T cell immune regulation of cytotoxic lymphocytes and macrophages allowing unregulated and spiraling immune activation and a "cytokine storm". Activated macrophages accumulate resulting in hemophagocytosis and organ damage. Patients often present, as ours did, with an infection of unknown origin and fevers, hepatitis, coagulopathy, cytopenias, hepatosplenomegaly, neurologic symptoms such as ataxia, and rash.
HLH remains a difficult diagnosis to make and even more difficult to treat. We hope ongoing efforts and research will continue towards understanding this often fatal disease.
References